☆ 4.6 Review

Molecular determinants of immunogenic cell death elicited by radiation therapy

IMMUNOLOGICAL REVIEWS (2023)

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Article Oncology

Radiotherapy combined with nivolumab or temozolomide for newly diagnosed glioblastoma with unmethylated MGMT promoter: An international randomized phase III trial

Antonio Omuro et al.

Summary: This study showed that TMZ + RT had better efficacy than NIVO + RT in newly diagnosed GBM patients with unmethylated MGMT promoter. However, no new safety signals were detected with NIVO in this study.

NEURO-ONCOLOGY (2023)

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Review Immunology

Immunogenic cell death: The cornerstone of oncolytic viro-immunotherapy

Lalitha Palanivelu et al.

Summary: Cancer is a major global health concern, causing millions of deaths each year. Traditional chemotherapy has limitations such as drug resistance and off-target effects, and cancer cells often develop ways to evade immune surveillance. However, oncolytic viro-immunotherapy can trigger immunogenic cell death (ICD), leading to an antitumor immune response. Oncolytic viruses can infect and destroy targeted cancer cells, stimulate the immune system, and release neoantigens to enhance antitumor immunity. This review discusses the concept of ICD in cancer and strategies to enhance the immunogenicity of oncolytic viruses.

FRONTIERS IN IMMUNOLOGY (2023)

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Article Oncology

Intratumoral BO-112 in combination with radiotherapy synergizes to achieve CD8 T-cell-mediated local tumor control

Maria E. Rodriguez-Ruiz et al.

Summary: This study demonstrates that local BO-112 immunotherapy and focal irradiation can synergistically achieve local tumor control. Furthermore, irradiation plus BO-112 in one of the tumor lesions enhances the therapeutic effects on distant irradiated lesions that were not injected with BO-112.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2023)

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Review Biochemistry & Molecular Biology

Apoptotic cell death in disease-Current understanding of the NCCD 2023

Ilio Vitale et al.

Summary: Apoptosis is a regulated cell death process involving caspase family proteases. Inhibiting or delaying apoptosis experimentally through pharmacological and genetic strategies has demonstrated its importance in embryonic development, tissue homeostasis, and the pathogenesis of various human disorders. Defects in apoptotic cell death machinery impair development and promote oncogenesis, while inappropriate activation of apoptosis contributes to cell loss and tissue damage in neurological, cardiovascular, renal, hepatic, infectious, neoplastic, and inflammatory conditions.

CELL DEATH AND DIFFERENTIATION (2023)

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Review Medicine, Research & Experimental

Immunogenic cell death in cancer: concept and therapeutic implications

Lorenzo Galluzzi et al.

Summary: Mammalian cells can undergo regulated cell death in response to specific disruptions of homeostasis, leading to adaptive immune responses. This immunogenic cell death (ICD) is distinct from immunostimulation or inflammatory responses that do not depend on cellular demise. In this article, we critically discuss the key concepts and mechanisms of ICD and its implications for cancer immunotherapy.

JOURNAL OF TRANSLATIONAL MEDICINE (2023)

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Article Multidisciplinary Sciences

The NK cell receptor NKp46 recognizes ecto-calreticulin on ER-stressed cells

Sumit Sen Santara et al.

Summary: Natural killer (NK) cells can recognize externalized calreticulin (ecto-CRT) as an endogenous ligand for the activating receptor NKp46. Recognition of ecto-CRT by NKp46 triggers NK cell signaling and leads to the elimination of ER-stressed cells. This recognition mechanism plays a crucial role in immune surveillance and cancer prevention.

NATURE (2023)

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Review Oncology

Emerging evidence for adapting radiotherapy to immunotherapy

Lorenzo Galluzzi et al.

Summary: Radiotherapy has potential synergistic effects with immunotherapy, but clinical trials have not shown clear improvements in patient outcomes. This review proposes that adapting radiotherapy regimens to immunotherapy may enhance the immune response and lead to meaningful clinical benefits.

NATURE REVIEWS CLINICAL ONCOLOGY (2023)

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Review Oncology

Antigen presentation in cancer - mechanisms and clinical implications for immunotherapy

Kailin Yang et al.

Summary: Immune-checkpoint inhibitors and other immunotherapies have revolutionized cancer treatment, but most patients do not derive durable benefit, indicating a need for biomarkers. This review explores the role of antigen presentation and molecular/genomic alterations affecting it in response to these therapies. Understanding the mechanisms of clinical response and resistance is essential for maximizing the clinical benefits of immunotherapies.

NATURE REVIEWS CLINICAL ONCOLOGY (2023)

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Review Cell Biology

Autophagy and autophagy-related pathways in cancer

Jayanta Debnath et al.

Summary: Autophagy plays both tumour-suppressive and tumour-promoting roles in cancer, depending on disease stage and mutational background. It is crucial for maintaining cellular homeostasis and cell viability by degrading and recycling cellular cargoes. Recent studies have also revealed its functions in the tumour microenvironment and immune cells, as well as the existence of autophagy-related pathways that contribute to malignant disease. Understanding the impact of autophagy on cancer development and progression has informed the development of anticancer therapies targeting autophagy processes.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2023)

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Article Multidisciplinary Sciences

STING agonist-loaded, CD47/PD-L1-targeting nanoparticles potentiate antitumor immunity and radiotherapy for glioblastoma

Peng Zhang et al.

Summary: The study describes the use of a bridging-lipid nanoparticle (B-LNP) that engages tumor-associated myeloid cells (TAMCs) to glioblastoma cells via anti-CD47/PD-L1 dual ligation. The B-LNPs block CD47 and PD-L1, promote TAMC phagocytic activity, and enhance T cell recruitment and antitumor responses. The administration of B-LNP/diABZI combined with radiotherapy promotes brain tumor regression and induces immunological memory against glioma.

NATURE COMMUNICATIONS (2023)

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Review Oncology

The DNA Damage Response and Infl ammation in Cancer

Vanessa Klapp et al.

Summary: Genomic stability is vital for normal cells to prevent oncogenesis. The DNA damage response (DDR) plays a role as a tumor suppressor protein in preserving genomic stability, inducing the death of cells with unrepairable DNA lesions and engaging cell-extrinsic oncosuppression through immunosurveillance. However, DDR signaling in cancer cells can inhibit tumor-targeting immune responses, favoring tumor progression and therapy resistance. This article discusses the complex interactions between DDR and inflammation in the context of oncogenesis, tumor progression, and response to therapy.

CANCER DISCOVERY (2023)

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Article Immunology

Immunogenic cell death after combined treatment with radiation and ATR inhibitors is dually regulated by apoptotic caspases

Adrian Eek Mariampillai et al.

Summary: ATR inhibitors can enhance the expression of immunogenic cell death (ICD) markers in irradiated cancer cells, while caspase activation regulates this response.

FRONTIERS IN IMMUNOLOGY (2023)

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Review Oncology

Dynamics and specificities of T cells in cancer immunotherapy

Giacomo Oliveira et al.

Summary: Recent advances in cancer immunotherapy have revolutionized cancer treatment, but there is variability in patient responses. Single-cell technologies have allowed us to study the characteristics and antigen specificity of tumor-specific T cells, providing insights into the mechanisms of effective cancer immunotherapy and guiding the development of more efficacious treatment strategies.

NATURE REVIEWS CANCER (2023)

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Review Oncology

Nucleotide metabolism: a pan-cancer metabolic dependency

Nicholas J. J. Mullen et al.

Summary: Metabolic alterations, specifically the augmented synthesis and use of nucleotide triphosphates, are crucial for cancer cells and contribute to their aggressive behaviors and resistance to therapies. Upregulation of nucleotide biosynthesis is a prerequisite for cancer initiation and progression. Despite the potential of nucleotide synthesis inhibitors, their full efficacy has not been realized. This review discusses recent studies on the diverse roles of hyperactive nucleotide metabolism in cancer and explores opportunities for combination therapies to target these pathways effectively.

NATURE REVIEWS CANCER (2023)

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Review Oncology

Therapeutic targeting of tumour myeloid cells

Simon T. Barry et al.

Summary: Myeloid cells in the tumour microenvironment have a significant impact on tumour progression, making them a key target for clinical therapies. However, large-scale clinical trials targeting these cells have had limited success. Understanding the specific functions and roles of different myeloid cell subpopulations within the tumour microenvironment could improve the design of successful clinical trials for myeloid-targeting therapies.

NATURE REVIEWS CANCER (2023)

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Review Immunology

TGFβ control of immune responses in cancer: a holistic immuno-oncology perspective

Briana G. Nixon et al.

Summary: In this Review, the authors discuss the diverse ways in which the cytokine transforming growth factor-beta (TGF beta) regulates immune responses to tumors, as well as the potential of targeting TGF beta for cancer therapy. The complex roles of TGF beta in tumor-induced immune responses and its contextual signaling in cancer cells and tumor stromal cells require rigorous experimental systems to understand the underlying immunobiology. The multiple functions of TGF beta in healthy tissues further complicate the search for effective and safe cancer therapeutics targeting the TGF beta pathway.

NATURE REVIEWS IMMUNOLOGY (2023)

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Review Immunology

Mitochondrial control of inflammation

Saverio Marchi et al.

Summary: This article discusses the molecular mechanisms by which mitochondrial dysfunction leads to inflammatory reactions, the cellular pathways that regulate them, and the pathological consequences of dysregulated inflammatory responses elicited by mitochondrial damage-associated molecular patterns (DAMPs).

NATURE REVIEWS IMMUNOLOGY (2023)

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Article Oncology

Sugemalimab versus placebo after concurrent or sequential chemoradiotherapy in patients with locally advanced, unresectable, stage III non-small-cell lung cancer in China (GEMSTONE-301): interim results of a randomised, double-blind, multicentre, phase 3 trial

Qing Zhou et al.

Summary: The efficacy and safety of sugemalimab, an anti-PD-L1 antibody, were assessed in patients with unresectable stage III non-small-cell lung cancer (NSCLC) who had not progressed after concurrent or sequential chemoradiotherapy. The results showed that sugemalimab significantly prolonged progression-free survival in these patients.

LANCET ONCOLOGY (2022)

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Review Immunology

Immunogenic cell stress and death

Guido Kroemer et al.

Summary: Immunogenic cell death (ICD) plays an important role in therapy and disease, as dying mammalian cells release signals that interact with the host to determine the immunological correlates of cellular stress and death. ICD is crucial in immunosurveillance and is related to strategies evolved by pathogens and cancer cells. Additionally, normal cell death can also initiate antigen-specific immune responses.

NATURE IMMUNOLOGY (2022)

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Review Oncology

Radiotherapy as a tool to elicit clinically actionable signalling pathways in cancer

Giulia Petroni et al.

Summary: Targeted anticancer agents have been successful in inhibiting specific molecular alterations in cancer cells, while radiotherapy activates cytotoxic pathways and protective mechanisms that can enhance the efficacy of these agents. By promoting non-oncogene dependence on targetable signaling pathways, radiotherapy has the potential to benefit a greater number of patients who may not respond to targeted therapies alone.

NATURE REVIEWS CLINICAL ONCOLOGY (2022)

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Review Oncology

Mechanisms regulating PD-L1 expression in cancers and associated opportunities for novel small-molecule therapeutics

Hirohito Yamaguchi et al.

Summary: Antibodies targeting PD-1 or its ligand PD-L1 have greatly impacted cancer therapy by improving patient survival. Strategies to overcome resistance and understanding the underlying mechanisms of PD-L1 upregulation in malignancies are important. Small-molecule inhibitors show potential for targeting oncogenic pathways and modulating PD-L1 expression in cancer therapy.

NATURE REVIEWS CLINICAL ONCOLOGY (2022)

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Review Biotechnology & Applied Microbiology

Identification of neoantigens for individualized therapeutic cancer vaccines

Franziska Lang et al.

Summary: This Review discusses the use of tumor-specific neoantigens in anticancer vaccines and introduces the mechanisms of neoantigen T cell recognition, as well as computational approaches to predict which neoantigens might confer proficient antitumor immunity in patients. Individualized treatment approaches are required to harness the full potential of the unique cancer mutations in each patient. Computational algorithms and machine-learning tools can be used to identify mutations, prioritize T cell-recognized antigens, and design personalized vaccines for each patient.

NATURE REVIEWS DRUG DISCOVERY (2022)

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Review Biotechnology & Applied Microbiology

Pharmacological targeting of endoplasmic reticulum stress in disease

Stefan J. Marciniak et al.

Summary: Research on drug-like molecules targeting ER stress and UPR has made progress, but limitations still exist. Understanding these limitations is crucial for the development of these molecules into therapeutic drugs.

NATURE REVIEWS DRUG DISCOVERY (2022)

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Article Oncology

Dynamics of HMBG1 (High Mobility Group Box 1) during radiochemotherapy correlate with outcome of HNSCC patients

Kerstin Clasen et al.

Summary: HMGB1 has been identified as a potential marker for monitoring immunogenic cell death in patients with HNSCC undergoing radiochemotherapy. The levels of HMGB1 were found to be positively correlated with tumor volumes, CRP levels, infections, and grade three toxicity, suggesting its potential utility in predicting treatment outcomes and monitoring immunogenic responses.

STRAHLENTHERAPIE UND ONKOLOGIE (2022)

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Article Oncology

Near-infrared photoimmunotherapy induced tumor cell death enhances tumor dendritic cell migration

Taiki Moriya et al.

Summary: Near-infrared photoimmunotherapy (NIR-PIT) selectively kills tumor cells and induces a systemic anti-tumor immune response. This study shows that NIR-PIT enhances migration of tumor-infiltrating dendritic cells (Ti-DCs) to draining lymph nodes (dLNs) via ATP-P2X7 receptor and G alpha i protein-coupled receptor signaling pathways, promoting tumor antigen presentation and the induction of anti-tumor T cells in dLNs.

CANCER IMMUNOLOGY IMMUNOTHERAPY (2022)

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Review Biotechnology & Applied Microbiology

Targeting oncogene and non-oncogene addiction to inflame the tumour microenvironment

Giulia Petroni et al.

Summary: Immune checkpoint inhibitors (ICIs) have revolutionized the clinical management of multiple tumours, but only a few patients respond to ICIs. This article discusses the potential of targeting oncogene and non-oncogene addiction to enhance ICI sensitivity and convert immunologically 'cold' tumours into 'hot' lesions.

NATURE REVIEWS DRUG DISCOVERY (2022)

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Article Oncology

Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter

Michael Lim et al.

Summary: The study evaluated the addition of the immune checkpoint inhibitor nivolumab (NIVO) to radiotherapy (RT) + temozolomide (TMZ) in newly diagnosed glioblastoma patients and found that it did not improve survival in these patients.

NEURO-ONCOLOGY (2022)

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Article Oncology

Combination of OX40 Co-Stimulation, Radiotherapy, and PD-1 Inhibition in a Syngeneic Murine Triple-Negative Breast Cancer Model

Min Guk Han et al.

Summary: This experimental study investigates the efficacy of triple combination therapy (radiation, PD-1 blockade, and OX40 co-stimulation) in a mouse model of immunologically cold triple-negative breast cancer. The results show significant improvement in tumor control and survival, with changes in the immune cell repertoire in the tumor microenvironment.

CANCERS (2022)

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Review Biotechnology & Applied Microbiology

Macrophages as tools and targets in cancer therapy

Alberto Mantovani et al.

Summary: This review discusses the molecular mechanisms of macrophage reprogramming in the tumor microenvironment and provides an overview of macrophage-targeted therapies for cancer treatment.

NATURE REVIEWS DRUG DISCOVERY (2022)

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Article Immunology

ATR-mediated CD47 and PD-L1 up-regulation restricts radiotherapy-induced immune priming and abscopal responses in colorectal cancer

Rodney Cheng-En Hsieh et al.

Summary: Radiation therapy induces up-regulation of CD47 and PD-L1 through the ATR-mediated DNA repair signaling pathway in CRC cells, which limits TAA cross-presentation and immune activation. Combination therapy with anti-SIRP alpha and anti-PD-1 reverses immune resistance, promotes TAA cross-presentation and robust antitumor immune priming.

SCIENCE IMMUNOLOGY (2022)

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Article Oncology

Radiotherapy in combination with CD47 blockade elicits a macrophage-mediated abscopal effect

Yoko Nishiga et al.

Summary: The combination of radiotherapy and CD47 blockade has shown therapeutic efficacy in small cell lung cancer, with macrophages migrating and phagocytosing cancer cells at non-irradiated tumor sites. This combination improves local antitumor effects and also stimulates off-target abscopal effects that inhibit non-irradiated tumors.

NATURE CANCER (2022)

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Article Immunology

Type I IFNs promote cancer cell stemness by triggering the epigenetic regulator KDM1B

Martina Musella et al.

Summary: The study demonstrates that type I interferons can promote the formation of cancer stem cells by upregulating the chromatin remodeling factor KDM1B. Inhibition of KDM1B could potentially prevent stem cell expansion and increase the long-term benefit of therapy.

NATURE IMMUNOLOGY (2022)

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Article Immunology

PDIA3 epitope-driven immune autoreactivity contributes to hepatic damage in type 2 diabetes

Cristina C. Clement et al.

Summary: A diet rich in saturated fat and carbohydrates can cause chronic inflammation in the liver and other organs, leading to nonalcoholic steatohepatitis. This study found that lipotoxicity and glucotoxicity induced by a high-fat and high-fructose diet can promote abnormal immune reactions to PDIA3 in the liver, resulting in liver damage.

SCIENCE IMMUNOLOGY (2022)

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Review Oncology

Developing dietary interventions as therapy for cancer

Samuel R. Taylor et al.

Summary: This Review discusses metabolic alterations and vulnerabilities in different types of cancer, and suggests using dietary interventions in combination with pharmacologic therapies to target these changes. However, diet studies in cancer patients are rare and lack robust evidence. The article also explores how dietary strategies can be combined with pharmacological therapies in treating cancer.

NATURE REVIEWS CANCER (2022)

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Review Immunology

A guide to antigen processing and presentation

Novalia Pishesha et al.

Summary: This article provides an overview of antigen processing and presentation pathways, explaining how antigenic peptides are loaded onto MHC molecules for detection by T cells. These pathways are essential for adaptive immunity and involve several steps for acquiring and presenting antigens for T cell recognition.

NATURE REVIEWS IMMUNOLOGY (2022)

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Review Oncology

Context-dependent functions of pattern recognition receptors in cancer

Si Ming Man et al.

Summary: The immune system plays a critical role in cancer, and while the importance of adaptive immunity has been recognized and utilized in immunotherapy, the potential of innate immunity has not been fully exploited. Pattern recognition receptors (PRRs) have emerged as key regulators in the immune response to cancer, both in immune cells and cancer cells. Targeting PRRs shows promise in cancer drug development and biomarker discovery.

NATURE REVIEWS CANCER (2022)

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Review Oncology

Radiotherapy and immunotherapy: open questions and future strategies

Kelli B. Pointer et al.

Summary: Immune checkpoint blockade improves outcomes for some advanced or metastatic cancer patients, but many do not respond to this treatment. Recent clinical trials have focused on combining immune checkpoint blockade with radiation therapy. While some Phase III trials have shown improved survival, other Phase I/II/III trials have yielded inconclusive or negative results, but offer promising insights for future therapeutic strategies.

TRENDS IN CANCER (2022)

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Review Immunology

Regulation of the nucleic acid-sensing Toll-like receptors

Nicholas A. Lind et al.

Summary: Activation of nucleic acid-sensing Toll-like receptors is finely tuned to distinguish between self and foreign nucleic acids. The ligands for TLRs are mostly unique to microorganisms, but a subset can recognize nucleic acids present in both host and foreign microorganisms, potentially leading to self-recognition and autoimmune diseases. Research in defining the regulatory mechanisms for proper discrimination between foreign and self-nucleic acids by TLRs has revealed a complex array of mechanisms, categorized into compartmentalization, ligand availability, receptor expression, and signal transduction.

NATURE REVIEWS IMMUNOLOGY (2022)

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Review Immunology

Immunomodulation by radiotherapy in tumour control and normal tissue toxicity

Urszula M. Cytlak et al.

Summary: Radiotherapy has both direct cytotoxic effects on tumors and potential immunomodulatory effects on surrounding tissues, leading to chronic inflammation and organ dysfunction. This can impact the quality of life for cancer survivors.

NATURE REVIEWS IMMUNOLOGY (2022)

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Review Immunology

Interferon-γ: teammate or opponent in the tumour microenvironment?

Angela M. Gocher et al.

Summary: IFN gamma plays pleiotropic roles in the tumor microenvironment, acting as both a 'teammate' to promote antitumor immune responses and an 'opponent' promoting tumor growth and suppressing immune responses.

NATURE REVIEWS IMMUNOLOGY (2022)

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Review Immunology

Natural killer cells in antiviral immunity

Niklas K. Bjorkstrom et al.

Summary: This review explores the role of natural killer cells in acute and chronic viral infections, particularly focusing on insights from patients with primary immunodeficiencies. It also discusses the involvement of natural killer cells in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The review highlights the importance of NK cells in innate immune responses to viral infections and provides recent insights into their role in human studies.

NATURE REVIEWS IMMUNOLOGY (2022)

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Review Oncology

Immunomodulation by targeted anticancer agents

Giulia Petroni et al.

Summary: Targeted anticancer agents are designed to inhibit specific molecular alterations that support oncogenesis or tumor progression, but they may also have immunomodulatory effects that can influence therapeutic efficacy. Harnessing these effects could potentially lead to superior clinical outcomes.

CANCER CELL (2021)

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Article Oncology

Geographic Density of Linear Accelerators and Receipt of Radiation Therapy for Prostate Cancer

J.E. Bates et al.

INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS (2021)

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Article Medicine, Research & Experimental

Radiotherapy-exposed CD8+ and CD4+ neoantigens enhance tumor control

Claire Lhuillier et al.

Summary: Radiotherapy upregulates the expression of genes containing immunogenic mutations, enhancing the therapeutic efficacy of neoantigen vaccination by promoting the killing of tumor cells through CD8 and CD4 T cells. CD4 T cells produce Th1 cytokines to promote epitope spread, while utilizing radiation to enhance the ability of MHC molecules and death receptors on tumor cells.

JOURNAL OF CLINICAL INVESTIGATION (2021)

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Article Biochemistry & Molecular Biology

The injury response to DNA damage in live tumor cells promotes antitumor immunity

Ganapathy Sriram et al.

Summary: Creating a live, injured tumor cell adjuvant through DNA damage enhances the efficacy of immune checkpoint blockade treatment, offering a strategy to improve the therapeutic effects on tumor types that do not respond to ICB alone.

SCIENCE SIGNALING (2021)

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Article Immunology

Pleiotropic consequences of metabolic stress for the major histocompatibility complex class II molecule antigen processing and presentation machinery

Cristina C. Clement et al.

Summary: Hyperglycemia and hyperlipidemia in individuals with type II diabetes and related mouse models can lead to oxidative alterations in the major histocompatibility complex (MHC) class II antigen processing machinery, affecting endosomal processing efficiency and DM editing activity. These changes in MHC class II antigen presentation may contribute to complications in T2D.

IMMUNITY (2021)

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Article Oncology

Avelumab plus standard-of-care chemoradiotherapy versus chemoradiotherapy alone in patients with locally advanced squamous cell carcinoma of the head and neck: a randomised, double-blind, placebo-controlled, multicentre, phase 3 trial

Nancy Y Lee et al.

LANCET ONCOLOGY (2021)

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Article Medicine, General & Internal

Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer

Ronan J. Kelly et al.

Summary: In patients with resected esophageal or gastroesophageal junction cancer who had received neoadjuvant chemoradiotherapy, adjuvant therapy with nivolumab significantly improved disease-free survival compared to placebo.

NEW ENGLAND JOURNAL OF MEDICINE (2021)

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Review Biochemistry & Molecular Biology

ATP and cancer immunosurveillance

Oliver Kepp et al.

Summary: In the TME, intracellular ATP plays a critical role in bioenergetic metabolism, while extracellular ATP functions as a signal transducer, affecting biology dependent on receptor types, cell types, and regulatory circuitry activation status. Additionally, extracellular ATP is rapidly degraded, leading to the accumulation of metabolites with distinct biological effects.

EMBO JOURNAL (2021)

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Article Multidisciplinary Sciences

Infection-induced type I interferons critically modulate the homeostasis and function of CD8+ naive T cells

Mladen Jergovic et al.

Summary: Infections can lead to the expansion of a subpopulation of long-lived, Ly6C(+) CD8(+) Tn cells with accelerated effector function, depending on the action of IFN-I. This highlights the significant role of infection-driven IFN-I in regulating Tn homeostasis and function, with potential implications for immunotherapy.

NATURE COMMUNICATIONS (2021)

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Review Oncology

Targeting Cancer Heterogeneity with Immune Responses Driven by Oncolytic Peptides

Ilio Vitale et al.

Summary: The high heterogeneity among malignant cells poses a significant obstacle to the success of cancer therapy, calling for the development of approaches that can operate despite such intratumoral heterogeneity. Oncolytic peptides, with their ability to induce immunogenic cell death and robust anticancer immune responses independently of intratumoral heterogeneity, show promise as therapeutic tools.

TRENDS IN CANCER (2021)

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Review Oncology

Therapeutic cancer vaccines

Mansi Saxena et al.

Summary: Therapeutic cancer vaccines aim to induce tumor regression, eradicate minimal residual disease, establish lasting anti-tumor memory, and avoid non-specific or adverse reactions. However, challenges arise due to tumor-induced immunosuppression and immunoresistance, hindering the achievement of these goals.

NATURE REVIEWS CANCER (2021)

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Review Oncology

Autophagy in tumour immunity and therapy

Houjun Xia et al.

Summary: Autophagy plays a crucial role in cancer by influencing tumor progression, immune responses, and therapy outcomes. Modulating the autophagy pathway can enhance antitumor immune responses and improve treatment efficacy.

NATURE REVIEWS CANCER (2021)

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Review Oncology

Antigen presentation in cancer: insights into tumour immunogenicity and immune evasion

Suchit Jhunjhunwala et al.

Summary: This review discusses the importance of antigen presentation in the success of immune checkpoint inhibition therapy and mechanisms by which tumors evade immune recognition. Tumors evade immune recognition by modulating antigen expression and altering antigen presentation.

NATURE REVIEWS CANCER (2021)

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Review Oncology

Endoplasmic reticulum stress signals in the tumour and its microenvironment

Xi Chen et al.

Summary: This review explores how ER stress in the tumor microenvironment can influence the functions of cancer cells and immune cells, leading to vulnerabilities that could be targeted by emerging therapeutic strategies. The tightly regulated processes of protein handling, modification, and folding in the ER determine cell function and survival, and disruptions in ER homeostasis can result in a state of persistent ER stress with pro-tumoral effects in cancer cells and immunomodulatory effects in immune cells.

NATURE REVIEWS CANCER (2021)

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Review Cell Biology

Calreticulin and cancer

Jitka Fucikova et al.

Summary: CALR is a protein located in the endoplasmic reticulum that plays important roles in cellular processes and protein folding. It acts as a chaperone in healthy cells, assisting protein folding and supporting Ca2+-dependent processes, while also being exposed on the cell surface in cancer cells to promote immunogenic cell death. Loss-of-functionCALRmutations can promote oncogenesis by impairing cellular homeostasis and compromising natural and therapy-driven immunosurveillance.

CELL RESEARCH (2021)

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Article Hematology

Calreticulin exposure on malignant blasts correlates with improved natural killer cell-mediated cytotoxicity in acute myeloid leukemia patients

Iva Truxova et al.

HAEMATOLOGICA (2020)

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Article Oncology

Immunogenic cell death by neoadjuvant oxaliplatin and radiation protects against metastatic failure in high-risk rectal cancer

Simer J. Bains et al.

CANCER IMMUNOLOGY IMMUNOTHERAPY (2020)

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Review Immunology

Immunological impact of cell death signaling driven by radiation on the tumor microenvironment

Maria Esperanza Rodriguez-Ruiz et al.

NATURE IMMUNOLOGY (2020)

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Article Oncology

CD73 blockade enhances the local and abscopal effects of radiotherapy in a murine rectal cancer model

Hidenori Tsukui et al.

BMC CANCER (2020)

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Article Medicine, Research & Experimental

Inhibition of transcription by dactinomycin reveals a new characteristic of immunogenic cell stress

Juliette Humeau et al.

EMBO MOLECULAR MEDICINE (2020)

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Article Oncology

CD73 Blockade Promotes Dendritic Cell Infiltration of Irradiated Tumors and Tumor Rejection

Erik Wennerberg et al.

CANCER IMMUNOLOGY RESEARCH (2020)

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Review Oncology

Consensus guidelines for the definition, detection and interpretation of immunogenic cell death

Lorenzo Galluzzi et al.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2020)

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Article Multidisciplinary Sciences

Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I

Keisuke Yamamoto et al.

NATURE (2020)

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Article Immunology

Tumor cells suppress radiation-induced immunity by hijacking caspase 9 signaling

Chuanhui Han et al.

NATURE IMMUNOLOGY (2020)

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Review Oncology

Targeting apoptosis in cancer therapy

Benedito A. Carneiro et al.

NATURE REVIEWS CLINICAL ONCOLOGY (2020)

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Review Cell Biology

The clearance of dead cells by efferocytosis

Emilio Boada-Romero et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2020)

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Review Immunology

Nucleic Acid Sensors as Therapeutic Targets for Human Disease

Sarah M. McWhirter et al.

IMMUNITY (2020)

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Article Immunology

Mitochondrial DNA drives abscopal responses to radiation that are inhibited by autophagy

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Antitumoural immunity by virus-mediated immunogenic apoptosis inhibits metastatic growth of hepatocellular carcinoma

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Overexpression of high-mobility group box 1 correlates with tumor progression and poor prognosis in human colorectal carcinoma

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In Situ Vaccination With a TLR9 Agonist Induces Systemic Lymphoma Regression: A Phase I/II Study

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Autophagy regulates selective HMGB1 release in tumor cells that are destined to die

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Fractionated but Not Single-Dose Radiotherapy Induces an Immune-Mediated Abscopal Effect when Combined with Anti-CTLA-4 Antibody

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Activation of the NLRP3 inflammasome in dendritic cells induces IL-1β-dependent adaptive immunity against tumors

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Induction of immunological tolerance by apoptotic cells requires caspase-dependent oxidation of high-mobility group box-1 protein

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IFN-α skews monocytes into CD56+-expressing dendritic cells with potent functional activities in vitro and in vivo

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Increased expression of high mobility group box 1 (HMGB1) is associated with progression and poor prognosis in human nasopharyngeal carcinoma

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An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2008)

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'Tuning' of type I interferon-induced Jak-STAT1 signaling by calcium-dependent kinases in macrophages

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Letter Biochemistry & Molecular Biology

Calreticulin exposure is required for the immunogenicity of γ-irradiation and UVC light-induced apoptosis

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Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy

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Calreticulin exposure dictates the immunogenicity of cancer cell death

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Calreticulin, a molecular chaperone in the endoplasmic reticulum, modulates radiosensitivity of human glioblastoma U251MG cells

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The combination of ionizing radiation and peripheral vaccination produces long-term survival of mice bearing established invasive GL261 gliomas

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Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy

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Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death

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Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte

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The expression of cytotoxic mediators is altered in mononuclear cells of patients with melanoma and increased by interferon-α treatment

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Characterization of the type I interferon locus and identification of novel genes

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High mobility group box protein 1: An endogenous signal for dendritic cell maturation and Th1 polarization

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Release of chromatin protein HMGB1 by necrotic cells triggers inflammation

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